Overview

Mice homozygous for both Sele (selectin, endothelial cell) and Selp (selectin, platelet) mutations are viable and fertile. They are characterized by leukocytosis, spontaneous bacterial infections, dermatitis and defective leukocyte recruitment in many models of inflammation.

Donating Investigator

Dr. Richard Hynes, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Selp^tm1Hyn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Selp	selectin, platelet

Sele^tm1Hyn

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Sele	selectin, endothelial cell

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Cell Biology Research
Research Tools
Cardiovascular Research
Hematological Research
Developmental Biology Research

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for both the Sele^tm1Hyn Selp^tm1Hyn mutations are viable and fertile. They are characterized by leukocytosis, spontaneous bacterial infections, dermatitis and defective leukocyte recruitment in many models of inflammation.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

The Sele^tm1Hyn mutation was created by replacing the exons encoding the signal peptide, lectin domain, and a portion of the epidermal growth factor domain with a PGK-hygro cassette. To create the Selp^tm1Hyn mutation, a portion of exon 3 encoding 10 amino acids of a signal peptide and 27 amino acids of the lectin domain was deleted by the insertion of PGK-neo cassette. The two mutations were introduced and selected sequentially in 129S2/SvPas-derived D3 embryonic stem (ES) cells. This line has been backcrossed from a mixed C57BL/6 and 129P2 background to C57BL/6 for more than 10 generations.

Selected References

Frenette PS; Mayadas TN; Rayburn H; Hynes RO; Wagner DD. 1996. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 84(4):563-74PubMed: 8598043 MGI: J:31626

View All References

Genetics

Selp^tm1Hyn

Allele Symbol: Selp^tm1Hyn

Allele Name	targeted mutation 1, Richard Hynes
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	P-; P-selectin^-; P-Selp^-
Gene Symbol and Name	Selp, selectin, platelet
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	1
Molecular Note	A portion of exon 3 encoding 10 amino acids of a signal peptide and 27 amino acids of the lectin domain was replaced with a PGK-neo cassette. Mice were treated with lipopolysaccharide to augment the normally low levels of selectin in lung and liver tissue. A longer transcript, resulting from aberrant or cryptic splicing involving the neomycin cassette, was detected at low levels in mutant mice by Northern blot analysis. RT-PCR further confirmed the presence of low levels of transcript in homozygous mice. Immunofluorescence analysis of activated platelets and lung sections from homozygous mutant mice showed an absence of encoded protein. These results were further confirmed by flow cytometric analysis of activated platelets and metabolic labeling of lung tissue.
Mutations Made By	Dr. Richard Hynes, Massachusetts Institute of Technology

Sele^tm1Hyn

Allele Symbol: Sele^tm1Hyn

Allele Name	targeted mutation 1, Richard Hynes
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	E-selectin^-; Sele^-
Gene Symbol and Name	Sele, selectin, endothelial cell
Gene Synonym(s)
Strain of Origin	129S2/SvPas
Chromosome	1
Molecular Note	A modified D3 ES cell line heterozygous for the Selp^tm1Hyn allele was targeted a second time. The exons encoding the signal peptide, lectin domain, and a portion of the epidermal growth factor domain were replaced by the insertion of a PGK-hygro cassette. Both Northern and RT-PCR analysis revealed an absence of normal message for both genes in extracts from cardiac and pulmonary tissue of homozygous mutant mice. This targeted mutation occurred in cis with the Selp^tm1Hyn mutation. Due to their genomic proximity, the two null alleles should propagate together through the offspring.
Mutations Made By	Dr. Richard Hynes, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Selp^tm1Hyn related

Immunology, Inflammation and Autoimmunity Research
- Inflammation
- CD Antigens, Antigen Receptors, and Histocompatibility Markers

Genotype: Sele^tm1Hyn related

Cell Biology Research
- Defects in Cell Adhesion Molecules
Research Tools
- Cell Biology Research
- Immunology, Inflammation and Autoimmunity Research
- Metabolism Research
Cardiovascular Research
- Vascular Defects
  - defective leukocyte function
- Atherosclerosis
Hematological Research
- Hematopoietic Defects
- Immunological Defects
Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Immunodeficiency Associated with Other Defects
- Inflammation
Developmental Biology Research
- Defects in Cell Adhesion Molecules

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency Associated with Other Defects
- Inflammation
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
Research Tools
- Cell Biology Research
- Immunology, Inflammation and Autoimmunity Research
- Metabolism Research
Cardiovascular Research
- Atherosclerosis
- Vascular Defects
  - defective leukocyte function
Cell Biology Research
- Defects in Cell Adhesion Molecules
Developmental Biology Research
- Defects in Cell Adhesion Molecules
Hematological Research
- Hematopoietic Defects
- Immunological Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Sele^tm1Hyn/Sele^tm1Hyn Selp^tm1Hyn/Selp^tm1Hyn
involves: 129S2/SvPas

cellular phenotype

impaired leukocyte tethering or rolling
- leukocyte rolling along mesenteric venules is virtually absent in these mice
- the number of adhering leukocytes is 6-fold less than controls
- the velocity of the rare leukocyte that does bind is much greater than those in wld-type
- TNF pre-treatment leads to a slight increase in rolling though the rolling flux is 46-fold less than in controls

abnormal granulocyte differentiation
- neutrophilic granulocytes compromise most of the cells of the bone marrow with an average of 60% of cells containing the segmented bands and rings morphology as compared to 42% in wild-type mice

homeostasis/metabolism phenotype

abnormal cytokine level
- exhibit a 5-fold elevation in GM-CSF levels

increased circulating interleukin-3 level
- mice have 40-fold higher levels of circulating IL-3 than controls

immune system phenotype

increased neutrophil cell number
- neonates exhibit a 3.3-fold increase in neutrophil numbers
- more than 16-fold increase in mature polymorphonuclear neutrophils

increased susceptibility to bacterial infection
- show a high prevalence of spontaneous bacterial dermatitis with or without ulceration, with the majority of mutants 4 months or older developing dermatitis

abnormal myelopoiesis
- the myeloid to erythroid ratio is increased more than 5-fold in these mice
- myeloid precursor are more numerous in the bone marrow

impaired neutrophil recruitment
- fewer than expected neutrophils are found at the site of skin lesions
- neutrophil recruitment in an induced peritonitis model is reduced
- there is a five-fold impairment in the number of neutrophils recruited by thioglycollate injection

increased lymphocyte cell number
- lymphocyte numbers are increased 1.5-fold

spleen hyperplasia
- spleens contain 2-fold more cells

impaired leukocyte tethering or rolling
- leukocyte rolling along mesenteric venules is virtually absent in these mice
- the number of adhering leukocytes is 6-fold less than controls
- the velocity of the rare leukocyte that does bind is much greater than those in wld-type
- TNF pre-treatment leads to a slight increase in rolling though the rolling flux is 46-fold less than in controls

increased monocyte cell number
- monocyte numbers are increased 9.8-fold in the blood

abnormal cytokine level
- exhibit a 5-fold elevation in GM-CSF levels

increased circulating interleukin-3 level
- mice have 40-fold higher levels of circulating IL-3 than controls

increased eosinophil cell number
- eosinophil numbers are increased 6.3-fold

increased spleen red pulp amount
- expanded red pulp

increased spleen weight
- splenic weights are increased about 2-fold

increased leukocyte cell number
- there is a 3.9-fold elevation in the mean number of leukocytes in the blood

abnormal granulocyte differentiation
- neutrophilic granulocytes compromise most of the cells of the bone marrow with an average of 60% of cells containing the segmented bands and rings morphology as compared to 42% in wild-type mice

mortality/aging

premature death
- fatalities are seen in mutants older than 3 months of age that develop bacterial dermatitis

growth/size/body region phenotype

increased spleen weight
- splenic weights are increased about 2-fold

spleen hyperplasia
- spleens contain 2-fold more cells

hematopoietic system phenotype

abnormal definitive hematopoiesis
- differentiating myeloid precursors are significantly more numerous, however blast forms are not increased, and precursor cells from the erythroid lineage are less numerous in the bone marrow, resulting in a myeloid to erythroid ratio that is increased more than 5-fold
- e than 5-fold

extramedullary hematopoiesis
- 3 of 10 show evidence of extramedullary hematopoietic activity in the liver
- increased extramedullary hematopoietic activity in the spleen

increased eosinophil cell number
- eosinophil numbers are increased 6.3-fold

increased leukocyte cell number
- there is a 3.9-fold elevation in the mean number of leukocytes in the blood

increased neutrophil cell number
- more than 16-fold increase in mature polymorphonuclear neutrophils
- neonates exhibit a 3.3-fold increase in neutrophil numbers

increased spleen weight
- splenic weights are increased about 2-fold

abnormal granulocyte differentiation
- neutrophilic granulocytes compromise most of the cells of the bone marrow with an average of 60% of cells containing the segmented bands and rings morphology as compared to 42% in wild-type mice

impaired neutrophil recruitment
- neutrophil recruitment in an induced peritonitis model is reduced
- there is a five-fold impairment in the number of neutrophils recruited by thioglycollate injection
- fewer than expected neutrophils are found at the site of skin lesions

increased spleen red pulp amount
- expanded red pulp

impaired hematopoiesis
- precursor cells of the erythroid lineage are under represented in the bone marrow

increased lymphocyte cell number
- lymphocyte numbers are increased 1.5-fold

abnormal common myeloid progenitor cell morphology
- spleens contain increased numbers of CFU-GM

impaired leukocyte tethering or rolling
- TNF pre-treatment leads to a slight increase in rolling though the rolling flux is 46-fold less than in controls
- the velocity of the rare leukocyte that does bind is much greater than those in wld-type
- the number of adhering leukocytes is 6-fold less than controls
- leukocyte rolling along mesenteric venules is virtually absent in these mice

abnormal erythropoiesis
- erythropoiesis is partially translocated to the spleen

spleen hyperplasia
- spleens contain 2-fold more cells

abnormal myelopoiesis
- myeloid precursor are more numerous in the bone marrow
- the myeloid to erythroid ratio is increased more than 5-fold in these mice

increased monocyte cell number
- monocyte numbers are increased 9.8-fold in the blood

increased erythroid progenitor cell number
- the number of BFU-E in the spleen are significantly increased

Genotype: Sele^tm1Hyn/Sele^tm1Hyn Selp^tm1Hyn/Selp^tm1Hyn
involves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

impaired neutrophil recruitment
- numbers of neutrophils increased between 8- 24 hours post injection whereas in wild-type mice they decrease
- neutrophil influx in thioglycollate-induced peritonitis is inhibited at 2, 4, and 8 hours after injection compared to wild-type mice
- lower numbers of neutrophils are observed than those elicited from mice that are null homozygotes for just one gene

increased leukocyte cell number
- leukocyte numbers are increased about 50%

increased eosinophil cell number
- eosinophil numbers are about 7-fold higher in the blood

impaired eosinophil recruitment
- 2-fold fewer eosinophils are recruited to the peritoneum in response to ragweed allergen challenge

increased neutrophil cell number
- neutrophils numbers are increased around 5-fold

impaired leukocyte tethering or rolling
- a population of leukocytes that are "fast rollers" is evident in these mice that are not observed in wild-type mice
- rolling leukocytes are virtually absent within the mesenteric venules of mice treated with TNF
- there is a decrease of about half in the number of adhering leukocytes within these mesenteric venules

increased monocyte cell number
- monocyte number are increased about 4-fold

immune system phenotype

impaired neutrophil recruitment
- numbers of neutrophils increased between 8- 24 hours post injection whereas in wild-type mice they decrease
- lower numbers of neutrophils are observed than those elicited from mice that are null homozygotes for just one gene
- neutrophil influx in thioglycollate-induced peritonitis is inhibited at 2, 4, and 8 hours after injection compared to wild-type mice

increased leukocyte cell number
- leukocyte numbers are increased about 50%

impaired leukocyte tethering or rolling
- a population of leukocytes that are "fast rollers" is evident in these mice that are not observed in wild-type mice
- there is a decrease of about half in the number of adhering leukocytes within these mesenteric venules
- rolling leukocytes are virtually absent within the mesenteric venules of mice treated with TNF

increased monocyte cell number
- monocyte number are increased about 4-fold

increased neutrophil cell number
- neutrophils numbers are increased around 5-fold

increased eosinophil cell number
- eosinophil numbers are about 7-fold higher in the blood

impaired eosinophil recruitment
- 2-fold fewer eosinophils are recruited to the peritoneum in response to ragweed allergen challenge

cellular phenotype

impaired leukocyte tethering or rolling
- there is a decrease of about half in the number of adhering leukocytes within these mesenteric venules
- rolling leukocytes are virtually absent within the mesenteric venules of mice treated with TNF
- a population of leukocytes that are "fast rollers" is evident in these mice that are not observed in wild-type mice

References

Frenette PS; Mayadas TN; Rayburn H; Hynes RO; Wagner DD. 1996. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 84(4):563-74PubMed: 8598043 MGI: J:31626

Additional - Sele^tm1Hyn related

Additional - Selp^tm1Hyn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Selp
- Standard PCR:Sele
- Genotyping resources and troubleshooting
Breeding Considerations

When maintained as a live colony, homozygotes may be bred.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S2-Sele^tm1Hyn Selp^tm1Hyn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008437 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Sele<tm1Hyn> Heterozygous for Selp<tm1Hyn>

Related Products and Services

Frozen Mouse Embryo	B6.129S2-Sele<tm1Hyn> Selp<tm1Hyn>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S2-Sele<tm1Hyn> Selp<tm1Hyn>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129S2-Sele<tm1Hyn> Selp<tm1Hyn>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129S2-Sele<tm1Hyn> Selp<tm1Hyn>/J Frozen Embryo	$3373.50

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Selptm1Hyn

Allele Symbol: Selptm1Hyn

Seletm1Hyn

Allele Symbol: Seletm1Hyn

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Selptm1Hyn related

Genotype: Seletm1Hyn related

Mammalian Phenotype Terms by Genotype

Genotype: Seletm1Hyn/Seletm1Hyn Selptm1Hyn/Selptm1Hyninvolves: 129S2/SvPas

cellular phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

growth/size/body region phenotype

hematopoietic system phenotype

Genotype: Seletm1Hyn/Seletm1Hyn Selptm1Hyn/Selptm1Hyninvolves: 129S2/SvPas * C57BL/6

hematopoietic system phenotype

immune system phenotype

cellular phenotype

References

Additional - Seletm1Hyn related

Additional - Selptm1Hyn related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Selp^tm1Hyn

Allele Symbol: Selp^tm1Hyn

Sele^tm1Hyn

Allele Symbol: Sele^tm1Hyn

Genotype: Selp^tm1Hyn related

Genotype: Sele^tm1Hyn related

Genotype: Sele^tm1Hyn/Sele^tm1Hyn Selp^tm1Hyn/Selp^tm1Hyn
involves: 129S2/SvPas

Genotype: Sele^tm1Hyn/Sele^tm1Hyn Selp^tm1Hyn/Selp^tm1Hyn
involves: 129S2/SvPas * C57BL/6

Additional - Sele^tm1Hyn related

Additional - Selp^tm1Hyn related